The total tissue CoA, which is synthesized in mammalian tissues from the vitamin pantothenic acid, increases in the liver during overnight fast and in the alloxan diabetic rats to 3 times that the fed state, while the total CoA of heart decreases by 60 per cent under such conditions. The means by which the tissue levels of CoA are regulated will be determined by examining the concentration of total tissue CoA (fluorometric enzymatic assay), and of pantothenate and p-pantetheine (microbacteriological assay), the uptake of C14-pantothenate into tissues, and the rates of incorporation of C14-pantothenate and S35- Cysteine into CoA and its precursors in the hearts and liver of rats fasted and refed various diets and made diabetic with alloxan. Measurements will also be made in mitochondria rapidly isolated from the tissues to distinguish differences between mitochondrial and cytosolic CoA pools. Isolated liver cells and the perfused rat heart will be used to determine the function of the changes in CoA and the relationship of the changes in total CoA to the maximum flux through various metabolic pathways and to the distribution of CoA between the free sulfhydryl and acylated forms. In the heart such measurements will be used to determine whether the rapid decline of CoA and pantothenate in diabetes and overnight fast represents a metabolic impairment due to a deficiency of pantothenate and whether an increased nutritional supply of pantothenate will eliminate the fluctuations of total CoA in a way which is advantageous to the heart.